The renin-angiotensin system is one of the complicated mechanisms involved in blood pressure regulation. Renin, an enzyme produced in kidney, acts on the circulating protein angiotensinogen, produced in liver, to give a decapeptide, angiotensin I. Angiotensin I has no biologic activity and is the target of the angiotensin-converting enzyme (ACE), which is present in large quantities in lung.
ACE is a zinc ion mediated peptidyldipeptide hydrolase (EC 3.4.15.1). It catalyzes conversion of the inactive decapeptide angiotensin I to the potent vasocontrictor octapeptide angiotensin II, which also stimulates the release of aldosterone from the adrenal glands and leads to the sodium and water retention. ACE also catalyzes the inactivation of the naturally occurring vasodepressor bradykinin. The importance of these reactions in hypertensive disease has been clarified by the development of potent and specific inhibitors of ACE, e.g., lisinopril, elonapril, fosinopril and captopril. At present ACE inhibitors are an important class of therapeutic drags in treating hypertension.
The distribution, biotransformation, and excretion of the different ACE inhibitor drugs in animals has been studied with radiolabelled compounds. From these studies, it has been concluded that the kidney and liver show high levels of ACE inhibitor drugs, due to the excretory role of these organs; but that high amounts are also concentrated in lung tissue. The radiolabelling of the ACE inhibitor compounds, therefore, is a powerful tool to image those organs, in order to diagnose diseases such as essential hypertension, renal artery stenosis or diabetic nephropathy.
Positron-labelled ACE inhibitors (captopril) have been described, Hwang et al, J. Nucl. Med. 32 (9), September 1991, pp 1730-1737, and used to probe ACE activity in vivo by positron emission toniography (PET), but PET scanners are not as widely available as SPECT (single proton emission computed tomography) scanning technology. Thus, a need exists for radiolabelled ACE inhibitors as a diagnostic tool available in all nuclear medicine departments.